Skip to main content
Top
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Is detection of intraperitoneal exfoliated tumor cells after surgical resection of rectal cancer a prognostic factor of survival?

Authors: Christian Arstad, Paulo Refinetti, Annette Torgunrud Kristensen, Karl-Erik Giercksky, Per Olaf Ekstrøm

Published in: BMC Cancer | Issue 1/2017

Login to get access

Abstract

Background

The prognostic significance of free cancer cells detected in peritoneal fluid at the time of rectal surgery remains unclear. A substantial number of patients will develop metastatic disease even with successful local treatment. This prospective non-randomized study investigated the prognostic value of intraperitoneal free cancer cells harvested in peritoneal lavage after surgery for rectal cancer. Mutational hotspots in mitochondrial DNA were examined as potential molecular signatures to detect circulating intraperitoneal free cancer cells when present in primary tumor and in lavage.

Methods

Point mutations in mitochondrial DNA amplifications were determined in primary tumors and corresponding exfoliated intraperitoneal free cancer cells in lavage from 191 patients with locally advanced rectal cancer scheduled for radical treatment. Mitochondrial DNA target sequences were amplified by polymerase chain reaction and base substitutions were detected by denaturant, cycling temperature capillary electrophoresis. Detection of intraperitoneal free cancer cells was correlated to survival.

Results

Of 191patients analyzed, 138 (72%) were identified with somatic mitochondrial point mutations in rectal cancer tumors. From this fraction, 45 patients (33%) had positive lavage fluid with corresponding somatic mtDNA point mutations in lavage representing circulating intraperitoneal free cancer cells. There was no significant survival difference between patients identified with or without somatic mitochondrial DNA point mutations in the corresponding lavage.

Conclusion

Somatic mitochondrial DNA point mutations identified in primary rectal tumors enable detection of circulating intraperitoneal free cancer cells in lavage fluid.
Intraperitoneal free cancer cells harvested from lavage immediately after surgery for rectal cancer does not represent an independent prognostic factor on survival.
Literature
2.
go back to reference Valentini V, Beets-Tan R, Borras JM, Krivokapic Z, Leer JW, Pahlman L, et al. Evidence and research in rectal cancer. Radiother Oncol. 2008;87(3):449–74.CrossRefPubMed Valentini V, Beets-Tan R, Borras JM, Krivokapic Z, Leer JW, Pahlman L, et al. Evidence and research in rectal cancer. Radiother Oncol. 2008;87(3):449–74.CrossRefPubMed
3.
go back to reference Kusters M, Marijnen CA, van de Velde CJ, Rutten HJ, Lahaye MJ, Kim JH, et al. Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial. Eur J Surg Oncol. 2010;36(5):470–6.CrossRefPubMed Kusters M, Marijnen CA, van de Velde CJ, Rutten HJ, Lahaye MJ, Kim JH, et al. Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial. Eur J Surg Oncol. 2010;36(5):470–6.CrossRefPubMed
4.
go back to reference Segelman J, Granath F, Holm T, Machado M, Mahteme H, Martling A. Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer. Br. J. Surg. 2012;99(5):699–705.CrossRefPubMed Segelman J, Granath F, Holm T, Machado M, Mahteme H, Martling A. Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer. Br. J. Surg. 2012;99(5):699–705.CrossRefPubMed
5.
go back to reference Lowe E, McKenna H. Peritoneal washing cytology: a retrospective analysis of 175 gynaecological patients. Aust N Z J Obstet Gynaecol. 1989;29(1):55–61.CrossRefPubMed Lowe E, McKenna H. Peritoneal washing cytology: a retrospective analysis of 175 gynaecological patients. Aust N Z J Obstet Gynaecol. 1989;29(1):55–61.CrossRefPubMed
6.
go back to reference Ziselman EM, Harkavy SE, Hogan M, West W, Atkinson B. Peritoneal washing cytology. Uses and diagnostic criteria in gynecologic neoplasms. Acta Cytol. 1984;28(2):105–10.PubMed Ziselman EM, Harkavy SE, Hogan M, West W, Atkinson B. Peritoneal washing cytology. Uses and diagnostic criteria in gynecologic neoplasms. Acta Cytol. 1984;28(2):105–10.PubMed
7.
go back to reference Colgan TJ, Boerner SL, Murphy J, Cole DE, Narod S, Rosen B. Peritoneal lavage cytology: an assessment of its value during prophylactic oophorectomy. Gynecol Oncol. 2002;85(3):397–403.CrossRefPubMed Colgan TJ, Boerner SL, Murphy J, Cole DE, Narod S, Rosen B. Peritoneal lavage cytology: an assessment of its value during prophylactic oophorectomy. Gynecol Oncol. 2002;85(3):397–403.CrossRefPubMed
8.
go back to reference Nath J, Moorthy K, Taniere P, Hallissey M, Alderson D. Peritoneal lavage cytology in patients with oesophagogastric adenocarcinoma. Br. J. Surg. 2008;95(6):721–6.CrossRefPubMed Nath J, Moorthy K, Taniere P, Hallissey M, Alderson D. Peritoneal lavage cytology in patients with oesophagogastric adenocarcinoma. Br. J. Surg. 2008;95(6):721–6.CrossRefPubMed
9.
go back to reference Iitsuka Y, Shiota S, Matsui T, Murata Y, Kimura A, Koga S. Relationship between the cytologic characteristics of intraperitoneal free cancer cells and the prognosis in patients with gastric cancer. Acta Cytol. 1990;34(3):437–42.PubMed Iitsuka Y, Shiota S, Matsui T, Murata Y, Kimura A, Koga S. Relationship between the cytologic characteristics of intraperitoneal free cancer cells and the prognosis in patients with gastric cancer. Acta Cytol. 1990;34(3):437–42.PubMed
10.
go back to reference Boku T, Nakane Y, Minoura T, Takada H, Yamamura M, Hioki K, et al. Prognostic significance of serosal invasion and free intraperitoneal cancer cells in gastric cancer. Br. J. Surg. 1990;77(4):436–9.CrossRefPubMed Boku T, Nakane Y, Minoura T, Takada H, Yamamura M, Hioki K, et al. Prognostic significance of serosal invasion and free intraperitoneal cancer cells in gastric cancer. Br. J. Surg. 1990;77(4):436–9.CrossRefPubMed
11.
go back to reference Bonenkamp JJ, Songun I, Hermans J, van de Velde CJ. Prognostic value of positive cytology findings from abdominal washings in patients with gastric cancer. Br. J. Surg. 1996;83(5):672–4.CrossRefPubMed Bonenkamp JJ, Songun I, Hermans J, van de Velde CJ. Prognostic value of positive cytology findings from abdominal washings in patients with gastric cancer. Br. J. Surg. 1996;83(5):672–4.CrossRefPubMed
12.
13.
go back to reference Sibio S, Fiorani C, Stolfi C, Divizia A, Pezzuto R, Montagnese F, et al. Detection methods and clinical significance of free peritoneal tumor cells found during colorectal cancer surgery. World JGastrointest Surg. 2015;7(9):178–84.CrossRef Sibio S, Fiorani C, Stolfi C, Divizia A, Pezzuto R, Montagnese F, et al. Detection methods and clinical significance of free peritoneal tumor cells found during colorectal cancer surgery. World JGastrointest Surg. 2015;7(9):178–84.CrossRef
14.
go back to reference Skipper D, Cooper AJ, Marston JE, Taylor I. Exfoliated cells and in vitro growth in colorectal cancer. Br. J. Surg. 1987;74(11):1049–52.CrossRefPubMed Skipper D, Cooper AJ, Marston JE, Taylor I. Exfoliated cells and in vitro growth in colorectal cancer. Br. J. Surg. 1987;74(11):1049–52.CrossRefPubMed
15.
go back to reference Umpleby HC, Fermor B, Symes MO, Williamson RC. Viability of exfoliated colorectal carcinoma cells. Br J Surg. 1984;71(9):659–63.CrossRefPubMed Umpleby HC, Fermor B, Symes MO, Williamson RC. Viability of exfoliated colorectal carcinoma cells. Br J Surg. 1984;71(9):659–63.CrossRefPubMed
16.
go back to reference Kristensen AT, Wiig JN, Larsen SG, Giercksky KE, Ekstrom PO. Molecular detection (k-ras) of exfoliated tumour cells in the pelvis is a prognostic factor after resection of rectal cancer? BMC Cancer. 2008;8:213.CrossRefPubMedPubMedCentral Kristensen AT, Wiig JN, Larsen SG, Giercksky KE, Ekstrom PO. Molecular detection (k-ras) of exfoliated tumour cells in the pelvis is a prognostic factor after resection of rectal cancer? BMC Cancer. 2008;8:213.CrossRefPubMedPubMedCentral
17.
go back to reference Ekstrom PO, Bjorheim J, Thilly WG. Technology to accelerate pangenomic scanning for unknown point mutations in exonic sequences: cycling temperature capillary electrophoresis (CTCE). BMC Genet. 2007;8:54.CrossRefPubMedPubMedCentral Ekstrom PO, Bjorheim J, Thilly WG. Technology to accelerate pangenomic scanning for unknown point mutations in exonic sequences: cycling temperature capillary electrophoresis (CTCE). BMC Genet. 2007;8:54.CrossRefPubMedPubMedCentral
18.
go back to reference Ekstrom PO, Khrapko K, Li-Sucholeiki XC, Hunter IW, Thilly WG. Analysis of mutational spectra by denaturing capillary electrophoresis. Nat Protoc. 2008;3(7):1153–66.CrossRefPubMedPubMedCentral Ekstrom PO, Khrapko K, Li-Sucholeiki XC, Hunter IW, Thilly WG. Analysis of mutational spectra by denaturing capillary electrophoresis. Nat Protoc. 2008;3(7):1153–66.CrossRefPubMedPubMedCentral
19.
go back to reference Steger G. Thermal denaturation of double-stranded nucleic acids: prediction of temperatures critical for gradient gel electrophoresis and polymerase chain reaction. Nucleic Acids Res. 1994;22(14):2760–8.CrossRefPubMedPubMedCentral Steger G. Thermal denaturation of double-stranded nucleic acids: prediction of temperatures critical for gradient gel electrophoresis and polymerase chain reaction. Nucleic Acids Res. 1994;22(14):2760–8.CrossRefPubMedPubMedCentral
21.
go back to reference Hase K, Ueno H, Kuranaga N, Utsunomiya K, Kanabe S, Mochizuki H. Intraperitoneal exfoliated cancer cells in patients with colorectal cancer. Dis Colon Rectum. 1998;41(9):1134–40.CrossRefPubMed Hase K, Ueno H, Kuranaga N, Utsunomiya K, Kanabe S, Mochizuki H. Intraperitoneal exfoliated cancer cells in patients with colorectal cancer. Dis Colon Rectum. 1998;41(9):1134–40.CrossRefPubMed
22.
go back to reference Vogel P, Ruschoff J, Kummel S, Zirngibl H, Hofstadter F, Hohenberger W, Jauch KW: Prognostic value of microscopic peritoneal dissemination: comparison between colon and gastric cancer. Dis Colon Rectum 2000, 43(1):92-100. Vogel P, Ruschoff J, Kummel S, Zirngibl H, Hofstadter F, Hohenberger W, Jauch KW: Prognostic value of microscopic peritoneal dissemination: comparison between colon and gastric cancer. Dis Colon Rectum 2000, 43(1):92-100.
23.
go back to reference Kanellos I, Demetriades H, Zintzaras E, Mandrali A, Mantzoros I, Betsis D. Incidence and prognostic value of positive peritoneal cytology in colorectal cancer. Dis Colon Rectum. 2003;46(4):535–9.CrossRefPubMed Kanellos I, Demetriades H, Zintzaras E, Mandrali A, Mantzoros I, Betsis D. Incidence and prognostic value of positive peritoneal cytology in colorectal cancer. Dis Colon Rectum. 2003;46(4):535–9.CrossRefPubMed
24.
go back to reference Salas A, Yao YG, Macaulay V, Vega A, Carracedo A, Bandelt HJ. A critical reassessment of the role of mitochondria in tumorigenesis. PLoS Med. 2005;2(11):e296.CrossRefPubMedPubMedCentral Salas A, Yao YG, Macaulay V, Vega A, Carracedo A, Bandelt HJ. A critical reassessment of the role of mitochondria in tumorigenesis. PLoS Med. 2005;2(11):e296.CrossRefPubMedPubMedCentral
25.
go back to reference Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, et al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science (New York, NY). 2010;328(5978):636–9.CrossRef Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, et al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science (New York, NY). 2010;328(5978):636–9.CrossRef
26.
27.
go back to reference Gundry M, Vijg J. Direct mutation analysis by high-throughput sequencing: from germline to low-abundant, somatic variants. Mutat Res. 2012;729(1–2):1–15.CrossRefPubMed Gundry M, Vijg J. Direct mutation analysis by high-throughput sequencing: from germline to low-abundant, somatic variants. Mutat Res. 2012;729(1–2):1–15.CrossRefPubMed
28.
go back to reference Wall JD, Tang LF, Zerbe B, Kvale MN, Kwok PY, Schaefer C, et al. Estimating genotype error rates from high-coverage next-generation sequence data. Genome Res. 2014;24(11):1734–9.CrossRefPubMedPubMedCentral Wall JD, Tang LF, Zerbe B, Kvale MN, Kwok PY, Schaefer C, et al. Estimating genotype error rates from high-coverage next-generation sequence data. Genome Res. 2014;24(11):1734–9.CrossRefPubMedPubMedCentral
29.
go back to reference Refinetti P, Morgenthaler S, Ekstrom PO. Cycling temperature capillary electrophoresis: a quantitative, fast and inexpensive method to detect mutations in mixed populations of human mitochondrial DNA. Mitochondrion. 2016;29:65–74.CrossRefPubMed Refinetti P, Morgenthaler S, Ekstrom PO. Cycling temperature capillary electrophoresis: a quantitative, fast and inexpensive method to detect mutations in mixed populations of human mitochondrial DNA. Mitochondrion. 2016;29:65–74.CrossRefPubMed
Metadata
Title
Is detection of intraperitoneal exfoliated tumor cells after surgical resection of rectal cancer a prognostic factor of survival?
Authors
Christian Arstad
Paulo Refinetti
Annette Torgunrud Kristensen
Karl-Erik Giercksky
Per Olaf Ekstrøm
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3365-7

Other articles of this Issue 1/2017

BMC Cancer 1/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine